Introduction: Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP). Methods: We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied. Results: Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = −0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = −0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable. Conclusions: Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.

1.
Sung
H
,
Ferlay
J
,
Siegel
RL
,
Laversanne
M
,
Soerjomataram
I
,
Jemal
A
,
.
Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries
.
CA Cancer J Clin
.
2021
;
71
(
3
):
209
49
.
2.
Schroder
FH
,
Hugosson
J
,
Roobol
MJ
,
Tammela
TLJ
,
Zappa
M
,
Nelen
V
,
.
Screening and prostate cancer mortality: results of the european randomised study of screening for prostate cancer (erspc) at 13 years of follow-up
.
Lancet
.
2014 Dec 6
;
384
(
9959
):
2027
35
.
3.
Kasivisvanathan
V
,
Rannikko
AS
,
Borghi
M
,
Panebianco
V
,
Mynderse
LA
,
Vaarala
MH
,
.
Mri-targeted or standard biopsy for prostate-cancer diagnosis
.
N Engl J Med
.
2018 May 10
;
378
(
19
):
1767
77
.
4.
Cohen
MS
,
Hanley
RS
,
Kurteva
T
,
Ruthazer
R
,
Silverman
ML
,
Sorcini
A
,
.
Comparing the gleason prostate biopsy and gleason prostatectomy grading system: the lahey clinic medical center experience and an international meta-analysis
.
Eur Urol
.
2008
;
54
(
2
):
371
81
.
5.
Zhou
J
,
Chen
H
,
Wu
Y
,
Shi
B
,
Ding
J
,
Qi
J
.
Plasma il 6 and tnfα levels correlate significantly with grading changes in localized prostate cancer
.
Prostate
.
2022
;
82
(
5
):
531
9
.
6.
Jang
WS
,
Koh
DH
,
Kim
J
,
Lee
JS
,
Chung
DY
,
Ham
WS
,
.
The prognostic impact of downgrading and upgrading from biopsy to radical prostatectomy among men with gleason score 7 prostate cancer
.
Prostate
.
2019 Dec
;
79
(
16
):
1805
10
.
7.
Haberal
HB
,
Artykov
M
,
Hazir
B
,
Citamak
B
,
Altan
M
,
Yazici
S
,
.
Predictors of isup score upgrade in patients with low-risk prostate cancer
.
Tumori
.
2021
;
107
(
3
):
254
60
.
8.
Gershman
B
,
Dahl
DM
,
Olumi
AF
,
Young
RH
,
McDougal
WS
,
Wu
CL
.
Smaller prostate gland size and older age predict gleason score upgrading
.
Urol Oncol
.
2013
;
31
(
7
):
1033
7
.
9.
Liberati
A
,
Altman
DG
,
Tetzlaff
J
,
Mulrow
C
,
Gotzsche
PC
,
Ioannidis
JPA
,
.
The prisma statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration
.
PLoS Med
.
2009 Jul 21
;
6
(
7
):
e1000100
.
10.
Stang
A
.
Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses
.
Eur J Epidemiol
.
2010
;
25
(
9
):
603
5
.
11.
Li
X
,
Wang
ZX
,
Zhu
YP
,
Wang
J
,
Yin
YS
,
Zeng
XY
.
Clinicopathological factors associated with pathological upgrading from biopsy to prostatectomy in patients with ISUP grade group ≤2 prostate cancer.
.
Asian J Androl
.
2022 Sep–Oct
;
24
(
5
):
487
93
.
12.
Salami
SS
,
Tosoian
JJ
,
Nallandhighal
S
,
Jones
TA
,
Brockman
S
,
Elkhoury
FF
,
.
Serial molecular profiling of low-grade prostate cancer to assess tumor upgrading: a longitudinal cohort study
.
Eur Urol
.
2021
;
79
(
4
):
456
65
.
13.
Zhang
B
,
Wu
S
,
Zhang
Y
,
Guo
M
,
Liu
R
.
Analysis of risk factors for gleason score upgrading after radical prostatectomy in a Chinese cohort
.
Cancer Med
.
2021
;
10
(
21
):
7772
80
.
14.
Karadağ
S
,
Ekşi
M
,
Ozdemir
O
,
Akkaş
F
,
Arikan
Y
,
Ozlu
DN
,
.
Is neutrophile to lymphocyte ratio a predictor of gleason score upgrading according to risk classifications in patients with prostate cancer
.
Arch Esp Urol
.
2021 Jul
;
74
(
6
):
599
605
.
15.
Kim
H
,
Kim
JK
,
Hong
SK
,
Jeong
CW
,
Ku
JH
,
Kwak
C
.
Role of multiparametric magnetic resonance imaging to predict postoperative gleason score upgrading in prostate cancer with gleason score 3 + 4
.
World J Urol
.
2021
;
39
(
6
):
1825
30
.
16.
Wang
X
,
Zhang
Y
,
Zhang
F
,
Ji
Z
,
Yang
P
,
Tian
Y
.
Predicting gleason sum upgrading from biopsy to radical prostatectomy pathology: a new nomogram and its internal validation
.
Bmc Urol
.
2021
;
21
(
1
):
3
.
17.
Alqahtani
S
,
Wei
C
,
Zhang
Y
,
Szewczyk-Bieda
M
,
Wilson
J
,
Huang
Z
,
.
Prediction of prostate cancer gleason score upgrading from biopsy to radical prostatectomy using pre-biopsy multiparametric mri pirads scoring system
.
Sci Rep
.
2020
;
10
(
1
):
7722
.
18.
Barsky
AR
,
Kraus
RD
,
Carmona
R
,
Santos
PMG
,
Li
C
,
Schwartz
LE
,
.
Investigating association of perineural invasion on prostate biopsy with gleason score upgrading at prostatectomy: a multi-institutional analysis
.
Cancer Med
.
2020
;
9
(
10
):
3383
9
.
19.
Pham
DM
,
Kim
JK
,
Lee
S
,
Hong
SK
,
Byun
SS
,
Lee
SE
.
Prediction of pathologic upgrading in gleason score 3+4 prostate cancer: who is a candidate for active surveillance
.
Investig Clin Urol
.
2020
;
61
(
4
):
405
10
.
20.
Ferro
M
,
Musi
G
,
Serino
A
,
Cozzi
G
,
Mistretta
FA
,
Costa
B
,
.
Neutrophil, platelets, and eosinophil to lymphocyte ratios predict gleason score upgrading in low-risk prostate cancer patients
.
Urol Int
.
2019
;
102
(
1
):
43
50
.
21.
Verep
S
,
Erdem
S
,
Ozluk
Y
,
Kilicaslan
I
,
Sanli
O
,
Ozcan
F
.
The pathological upgrading after radical prostatectomy in low risk prostate cancer patients who are eligible for active surveillance: how safe is it to depend on bioptic pathology
.
Prostate
.
2019
;
79
(
13
):
1523
9
.
22.
Zhai
L
,
Fan
Y
,
Sun
S
,
Wang
H
,
Meng
Y
,
Hu
S
,
.
Pi-rads v2 and periprostatic fat measured on multiparametric magnetic resonance imaging can predict upgrading in radical prostatectomy pathology amongst patients with biopsy gleason score 3 + 3 prostate cancer
.
Scand J Urol
.
2018
;
52
(
5–6
):
333
9
.
23.
Song
W
,
Bang
SH
,
Jeon
HG
,
Jeong
BC
,
Seo
SI
,
Jeon
SS
,
.
Role of pi-rads version 2 for prediction of upgrading in biopsy-proven prostate cancer with gleason score 6
.
Clin Genitourin Cancer
.
2018
;
16
(
4
):
281
7
.
24.
Santok
GDR
,
Abdel Raheem
A
,
Kim
LH
,
Chang
K
,
Lum
TG
,
Chung
BH
,
.
Prostate-specific antigen 10–20 ng/mL: a predictor of degree of upgrading to ≥8 among patients with biopsy gleason score 6
.
Investig Clin Urol
.
2017
;
58
(
2
):
90
7
.
25.
Porcaro
AB
,
Petroziello
A
,
Brunelli
M
,
De Luyk
N
,
Cacciamani
G
,
Corsi
P
,
.
High testosterone preoperative plasma levels independently predict biopsy gleason score upgrading in men with prostate cancer undergoing radical prostatectomy
.
Urol Int
.
2016
;
96
(
4
):
470
8
.
26.
Gao
Y
,
Jiang
CY
,
Mao
SK
,
Cui
D
,
Hao
KY
,
Zhao
W
,
.
Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy
.
Asian J Androl
.
2016 Jul–Aug
;
18
(
4
):
639
43
.
27.
Lotan
TL
,
Carvalho
FL
,
Peskoe
SB
,
Hicks
JL
,
Good
J
,
Fedor
H
,
.
Pten loss is associated with upgrading of prostate cancer from biopsy to radical prostatectomy
.
Mod Pathol
.
2015 Jan
;
28
(
1
):
128
37
.
28.
Jo
JK
,
Hong
SK
,
Byun
SS
,
Lee
SE
,
Oh
JJ
.
Comparison of clinical outcomes between upgraded pathologic gleason score 3 + 4 and non-upgraded 3 + 4 prostate cancer among patients who are candidates for active surveillance
.
World J Urol
.
2015
;
33
(
11
):
1729
34
.
29.
Hwang
I
,
Lim
D
,
Jeong
YB
,
Park
SC
,
Noh
JH
,
Kwon
DD
,
.
Upgrading and upstaging of low-risk prostate cancer among Korean patients: a multicenter study
.
Asian J Androl
.
2015 Sep–Oct
;
17
(
5
):
811
4
.
30.
Vora
A
,
Large
T
,
Aronica
J
,
Haynes
S
,
Harbin
A
,
Marchalik
D
,
.
Predictors of gleason score upgrading in a large african-american population
.
Int Urol Nephrol
.
2013
;
45
(
5
):
1257
62
.
31.
Fu
Q
,
Moul
JW
,
Bañez
LL
,
Sun
L
,
Mouraviev
V
,
Xie
D
,
.
Association between percentage of tumor involvement and gleason score upgrading in low-risk prostate cancer
.
Med Oncol
.
2012
;
29
(
5
):
3339
44
.
32.
Oh
JJ
,
Hong
SK
,
Lee
JK
,
Lee
BK
,
Lee
S
,
Kwon
OS
,
.
Prostate-specific antigen vs prostate-specific antigen density as a predictor of upgrading in men diagnosed with gleason 6 prostate cancer by contemporary multicore prostate biopsy
.
Bju Int
.
2012
;
110
(
11 Pt B
):
E494
99
.
33.
Epstein
JI
,
Feng
Z
,
Trock
BJ
,
Pierorazio
PM
.
Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified gleason grading system and factoring in tertiary grades
.
Eur Urol
.
2012 May
;
61
(
5
):
1019
24
.
34.
Davies
JD
,
Aghazadeh
MA
,
Phillips
S
,
Salem
S
,
Chang
SS
,
Clark
PE
,
.
Prostate size as a predictor of gleason score upgrading in patients with low risk prostate cancer
.
J Urol
.
2011
;
186
(
6
):
2221
7
.
35.
Sooriakumaran
P
,
Srivastava
A
,
Christos
P
,
Grover
S
,
Shevchuk
M
,
Tewari
A
.
Predictive models for worsening prognosis in potential candidates for active surveillance of presumed low-risk prostate cancer
.
Int Urol Nephrol
.
2012
;
44
(
2
):
459
70
.
36.
Chun
FKH
,
Steuber
T
,
Erbersdobler
A
,
Currlin
E
,
Walz
J
,
Schlomm
T
,
.
Development and internal validation of a nomogram predicting the probability of prostate cancer gleason sum upgrading between biopsy and radical prostatectomy pathology
.
Eur Urol
.
2006
;
49
(
5
):
820
6
.
37.
Boorjian
SA
,
Karnes
RJ
,
Crispen
PL
,
Rangel
LJ
,
Bergstralh
EJ
,
Sebo
TJ
,
.
The impact of discordance between biopsy and pathological gleason scores on survival after radical prostatectomy
.
J Urol
.
2009
;
181
(
1
):
95
104
; discussion 104. https://doi.org/10.1016/j.juro.2008.09.016.
38.
Heidenreich
A
,
Bastian
PJ
,
Bellmunt
J
,
Bolla
M
,
Joniau
S
,
van der Kwast
T
,
.
Eau guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013
.
Eur Urol
.
2014
;
65
(
1
):
124
37
.
39.
Sarici
H
,
Telli
O
,
Yigitbasi
O
,
Ekici
M
,
Ozgur
BC
,
Yuceturk
CN
,
.
Predictors of gleason score upgrading in patients with prostate biopsy gleason score ≤6
.
Can Urol Assoc J
.
2014
;
8
(
5–6
):
E342
46
.
40.
Kundu
SD
,
Roehl
KA
,
Yu
X
,
Antenor
JAV
,
Suarez
BK
,
Catalona
WJ
.
Prostate specific antigen density correlates with features of prostate cancer aggressiveness
.
J Urol
.
2007
;
177
(
2
):
505
9
.
41.
Freedland
SJ
,
Amling
CL
,
Dorey
F
,
Kane
CJ
,
Presti
JC
,
Terris
MK
,
.
Race as an outcome predictor after radical prostatectomy: results from the shared equal access regional cancer hospital (search) database
.
Urology
.
2002 2002
;
60
(
4
):
670
4
.
42.
Hong
SK
,
Han
BK
,
Lee
ST
,
Kim
SS
,
Min
KE
,
Jeong
SJ
,
.
Prediction of Gleason score upgrading in low-risk prostate cancers diagnosed via multi (> or = 12)-core prostate biopsy
.
World J Urol
.
2009
;
27
(
2
):
271
6
.
43.
Freedland
SJ
,
Isaacs
WB
,
Platz
EA
,
Terris
MK
,
Aronson
WJ
,
Amling
CL
,
.
Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study
.
J Clin Oncol
.
2005 Oct 20
;
23
(
30
):
7546
54
.
44.
de Cobelli
O
,
Terracciano
D
,
Tagliabue
E
,
Raimondi
S
,
Galasso
G
,
Cioffi
A
,
.
Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance
.
Urol Oncol
.
2015
;
33
(
5
):
201.e1
201.e8
.
45.
Erdem
S
,
Verep
S
,
Bagbudar
S
,
Ozluk
Y
,
Sanli
O
,
Ozcan
F
.
The clinical predictive factors and postoperative histopathological parameters associated with upgrading after radical prostatectomy: a contemporary analysis with grade groups
.
Prostate
.
2020
;
80
(
2
):
225
34
.
46.
Ng
JC
,
Koch
MO
,
Daggy
JK
,
Cheng
L
.
Perineural invasion in radical prostatectomy specimens: lack of prognostic significance
.
J Urol
.
2004
;
172
(
6 Pt 1
):
2249
51
.
47.
Sun
G
,
Huang
R
,
Zhang
X
,
Shen
P
,
Gong
J
,
Zhao
J
,
.
The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen-deprivation therapy in high-risk prostate cancer following radical prostatectomy
.
Prostate
.
2017 Sep
;
77
(
12
):
1279
87
.
48.
Grivennikov
SI
,
Greten
FR
,
Karin
M
.
Immunity, inflammation, and cancer
.
Cell
.
2010 Mar 19
;
140
(
6
):
883
99
.
49.
Lee
YS
,
Nam
HS
,
Lim
JH
,
Kim
JS
,
Moon
Y
,
Cho
JH
,
.
Prognostic impact of a new score using neutrophil-to-lymphocyte ratios in the serum and malignant pleural effusion in lung cancer patients
.
Bmc Cancer
.
2017
;
17
(
1
):
557
.
50.
Gokce
MI
,
Hamidi
N
,
Suer
E
,
Tangal
S
,
Huseynov
A
,
Ibiş
A
.
Evaluation of neutrophil-to-lymphocyte ratio prior to prostate biopsy to predict biopsy histology: results of 1836 patients
.
Can Urol Assoc J
.
2015 Nov–Dec
;
9
(
11–12
):
E761
65
.
51.
Ploussard
G
,
Isbarn
H
,
Briganti
A
,
Sooriakumaran
P
,
Surcel
CI
,
Salomon
L
,
.
Can we expand active surveillance criteria to include biopsy gleason 3+4 prostate cancer? A multi-institutional study of 2, 323 patients
.
Urol Oncol
.
2015
;
33
(
2
):
71.e1
71.e9
.
You do not currently have access to this content.